SAFETY AND TOLERABILITY OF CYCLOSPORINE AND CYCLOSPORINE MICROEMULSION DURING 18 MONTHS OF FOLLOW-UP IN STABLE RENAL-TRANSPLANT RECIPIENTS - A REPORT OF THE CANADIAN NEORAL RENAL STUDY-GROUP

Background. There has been concern that the increased drug exposure as sociated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events. Methods. The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were co mpared in a randomized, multicenter, pharmacoepidemiologic study invol ving 1097 stable renal transplant patients after 18 months of follow-u p. Results. No significant difference was seen in change in serum crea tinine or calculated creatinine clearance between the two groups. Epis odes of deterioration in renal function (change in serum creatinine gr eater than or equal to 20%) were categorized with the following result s for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.00 8); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During th e first 6 months of the study, a transient increase in the incidence o f gastrointestinal and neurological adverse events was seen in the CsA -ME group compared with the CsA group. Up to 18 months, patients in th e CsA group reported significantly fewer hearing and vestibular disord ers, but more cardiovascular problems than those in the CsA-ME group ( P=0.035). Conclusions. Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased dr ug exposure with CsA-ME, although there was a transient increase in ne phrotoxicity. The frequency of acute and chronic rejection did not cha nge.